P1694: COST-EFFECTIVENESS OF AXICABTAGENE CILOLEUCEL VS. TISAGENLECLEUCEL FOR THE TREATMENT OF RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA: UPDATED SURVIVAL RESULTS FROM THE ZUMA-1 AND JULIET TRIALS
Authors: Olalekan Oluwole, Markqayne Ray, Neil Davies, Rory Bradford, Calum Jones, Anik Patel, Frederick Locke
Journal: HemaSphere (2023)

Topic: 36. Ethics and health economics Background: Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are the first two chimeric-antigen receptor T-cell therapies approved for the treatment of adults with relapsed/refractory (R/R) large b-cell lymphoma (LBCL) after ≥2 prior systemic therapies. The safety and efficacy of axi-cel and tisa-cel in 3L+ R/R LBCL patients were assessed in open-label, single-arm, multicenter, phase II trials, ZUMA-1 and JULIET, respectively. In a cost-utility analysis with shorter follow-up of ZUMA-1 and JULIET, axi-cel demonstrated greater life years (LYs), an increase in quality-adjusted life years (QALYs) and reduced costs when compared to tisa-cel (Liu et al, J Med Econ, 2021). Since then, the two trials have showcased extended survival follow-up, with ZUMA-1 reporting survival outcomes with a median follow-up of 51.1 months and JULIET reporting survival outcomes with a median follow-up of 40.3 months. The median overall survival (OS) from the two trials was reported as 25.8 months and 11.1 months for axi-cel and tisa-cel, respectively. Aims: A cost-utility analysis was conducted to compare axi-cel with tisa-cel in 3L+ R/R LBCL, utilizing a previously conducted matching-adjusted indirect comparison (MAIC) (Oluwole et al, BBMT, 2020), and the most recent five-year follow-up survival data from the ZUMA-1 trial, and approximately four-year follow-up data from the JULIET trial. Methods: A three-state (i.e., pre-progression, post-progression and death) partitioned survival model was developed using a United States payer perspective over a lifetime time horizon, in accordance with established guidelines. Patients entered the model in the progression-free survival (PFS) state, and transitions to the progressed disease and death health states were managed by mixture-cure parametric models; OS was used to determine transitions to the death state. Survival estimates for the tisa-cel arm were generated from the updated JULIET follow-up. The OS and PFS curves for axi-cel were adjusted through a MAIC approach to account for the imbalance in baseline patient characteristics between the ZUMA-1 and JULIET populations. All associated costs in the model were reflective of 2022 United States Dollars. Following US cost-effectiveness standard practice, costs and outcomes were discounted at 3% per year. Results: Axi-cel was associated with an increase in LYs and QALYs compared to tisa-cel, 3.11 and 2.82 respectively (Figure 1). Axi-cel resulted in a total cost increase of $19,341 relative to tisa-cel, driven largely by difference in drug acquisition costs, despite higher post-progression costs for tisa-cel. This led to an incremental cost-effectiveness ratio of $6,847/QALY. Univariate sensitivity analysis indicated that drug acquisition costs of CAR T-cell therapies had the greatest impact on the costs per QALY gained, followed by the length of non-ICU inpatient stay and the cost of initial hospitalization inpatient days. Probabilistic sensitivity analysis (1,000 iterations) indicated that axi-cel had a 100% probability of cost-effectiveness at a willingness-to-pay threshold of $150,000 per QALY. Summary/Conclusion: Axi-cel is likely a cost-effective treatment, compared to tisa-cel, for the treatment of 3L+ R/R LBCL from a United States payer perspective. The longer-term survival follow-up data from the ZUMA-1 and JULIET trials have provided more robust evidence for use in the survival analyses than shorter follow-up data, thus reinforcing previous results and generating increased confidence in the findings.Keywords: Diffuse large B cell lymphoma, CAR-T, Cost effectiveness, relapsed/refractory